Publications

2021
Ithai Rabinowitch, Bishal Upadhyaya, Aaradhya Pant, Dolev Galski, Lena Kreines, and Jihong Bai. 2021. “Circumventing Neural Damage in a C. elegans Chemosensory Circuit Using Genetically Engineered Synapses.” Cell Systems. Publisher's Version Abstract
Neuronal loss can considerably diminish neural circuit function, impairing normal behavior by disrupting information flow in the circuit. Here, we use genetically engineered electrical synapses to reroute the flow of information in a C. elegans damaged chemosensory circuit in order to restore organism behavior. We impaired chemotaxis by removing one pair of interneurons from the circuit then artificially coupled two other adjacent neuron pairs by ectopically expressing the gap junction protein, connexin, in them. This restored chemotaxis in the animals. We expected to observe linear and direct information flow between the connexin-coupled neurons in the recovered circuit but also revealed the formation of new potent left-right lateral electrical connections within the connexin-expressing neuron pairs. Our analysis suggests that these additional electrical synapses help restore circuit function by amplifying weakened neuronal signals in the damaged circuit in addition to emulating the wild-type circuit. A record of this paper's transparent peer review process is included in the Supplemental Information.
A. Halaj and J.D. Huppert. 2021. “Clinical and Cognitive Insight in Pathological Anxiety: Relationship to Cognitive Factors and Implicit Theories.” International Journal of Cognitive Therapy, 14, Pp. 671-686.
Reut Itzkovitch Malka, Shaul Shenhav, Reuven Y. Hazan, and Gideon Rahat. 2021. “The Collective Memory of Dominant Parties in Parliamentary Discourse.” Party Politics, 27, 1, Pp. 489-500. Publisher's Version
Reut Itzkovitch Malka, Shaul R. Shenhav, Gideon Rahat, and Reuven Y. Hazan. 2021. “The collective memory of dominant parties in parliamentary discourse.” Party Politics, 27, 3, Pp. 489–500. Publisher's Version Abstract

When the past is contested by political actors, it can play a notable role both in present and in future politics. This is especially true when it comes to the memory of dominant parties, which are part and parcel of political and national history. Focusing on dominant parties in parliamentary democracies, this article examines the memory dynamics of a dominant party after its demise and highlights the importance of memory modes in understanding these dynamics. Using theories of collective memory, it identifies four possible modes of memory in a post-dominance era, suggesting discursive and power-related indications for each mode. The article then utilizes this framework to examine the memory of Mapai, the once-dominant party in Israel. On the basis of this analysis, the authors propose hypotheses concerning the comparative cases of Sweden, Italy, and Japan.

J.R. Church, A.G. Rao, A. Barnoy, C. Wiebeler, and I. Schapiro. 2021. Computational Studies of Photochemistry in Phytochrome Proteins, Pp. 197 - 226. Publisher's Version
Alexander Bespaly, Indranuj Dey, Jenya Papeer, Assaf Shaham, Pavel Komm, Ibrahim Hadad, Gilad Marcus, and Arie Zigler. 2021. “Control of amorphous solid water target morphology induced by deposition on a charged surface.” High Power Laser Science and Engineering, 9, Pp. e37.
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Elon Kohlberg and Abraham Neyman. 2021. “Cooperative Strategic Games.” Theoretical Economics , 16, Pp. 825--851. Abstract

The value is a solution concept for n-person strategic games, developed by Nash,
Shapley, and Harsanyi. The value of a game is an a priori evaluation of the economic
worth of the position of each player, reflecting the players’ strategic possibilities,
including their ability to make threats against one another. Applications of the value in economics have been rare, at least in part because the existing definition (for games with more than two players) consists of an ad hoc scheme that does not easily lend itself to computation. This paper makes three contributions: We provide an axiomatic foundation for the value; exhibit a simple formula for its computation; and extend the value—its definition, axiomatic characterization, and computational formula—to Bayesian games. We then apply the value in simple models of corruption, oligopolistic competition, and information sharing.

Published paper TE 2021.pdf Expanded version
Ilan Shumilin and Daniel Harries. 2021. “Cyclodextrin solubilization in hydrated reline: Resolving the unique stabilization mechanism in a deep eutectic solvent.” The Journal of Chemical Physics, 154, 22, Pp. 224505. Publisher's Version Abstract

By complexing with hydrophobic compounds, cyclodextrins afford increased solubility and thermodynamic stability to hardly soluble compounds, thereby underlining their invaluable applications in pharmaceutical and other industries. However, common cyclodextrins such as β-cyclodextrin, suffer from limited solubility in water, which often leads to precipitation and formation of unfavorable aggregates, driving the search for better solvents. Here, we study the solvation of cyclodextrin in deep eutectic solvents (DESs), environmentally friendly media that possess unique properties. We focus on reline, the DES formed from choline chloride and urea, and resolve the mechanism through which its constituents elevate β-cyclodextrin solubility in hydrated solutions compared to pure water or dry reline. Combining experiments and simulations, we determine that the remarkable solubilization of β-cyclodextrin in hydrated reline is mostly due to the inclusion of urea inside β-cyclodextrin’s cavity and at its exterior surfaces. The role of choline chloride in further increasing solvation is twofold. First, it increases urea’s solubility beyond the saturation limit in water, ultimately leading to much higher β-cyclodextrin solubility in hydrated reline in comparison to aqueous urea solutions. Second, choline chloride increases urea’s accumulation in β-cyclodextrin’s vicinity. Specifically, we find that the accumulation of urea becomes stronger at high reline concentrations, as the solution transitions from reline-in-water to water-in-reline, where water alone cannot be regarded as the solvent. Simulations further suggest that in dry DES, the mechanism of β-cyclodextrin solvation changes so that reline acts as a quasi-single component solvent that lacks preference for the accumulation of urea or choline chloride around β-cyclodextrin.

By complexing with hydrophobic compounds, cyclodextrins afford increased solubility and thermodynamic stability to hardly soluble compounds, thereby underlining their invaluable applications in pharmaceutical and other industries. However, common cyclodextrins such as β-cyclodextrin, suffer from limited solubility in water, which often leads to precipitation and formation of unfavorable aggregates, driving the search for better solvents. Here, we study the solvation of cyclodextrin in deep eutectic solvents (DESs), environmentally friendly media that possess unique properties. We focus on reline, the DES formed from choline chloride and urea, and resolve the mechanism through which its constituents elevate β-cyclodextrin solubility in hydrated solutions compared to pure water or dry reline. Combining experiments and simulations, we determine that the remarkable solubilization of β-cyclodextrin in hydrated reline is mostly due to the inclusion of urea inside β-cyclodextrin’s cavity and at its exterior surfaces. The role of choline chloride in further increasing solvation is twofold. First, it increases urea’s solubility beyond the saturation limit in water, ultimately leading to much higher β-cyclodextrin solubility in hydrated reline in comparison to aqueous urea solutions. Second, choline chloride increases urea’s accumulation in β-cyclodextrin’s vicinity. Specifically, we find that the accumulation of urea becomes stronger at high reline concentrations, as the solution transitions from reline-in-water to water-in-reline, where water alone cannot be regarded as the solvent. Simulations further suggest that in dry DES, the mechanism of β-cyclodextrin solvation changes so that reline acts as a quasi-single component solvent that lacks preference for the accumulation of urea or choline chloride around β-cyclodextrin.

 

Yael Ebert, Ron Shaar, and Mordechai Stein. 2021. “Decadal geomagnetic secular variations from greigite bearing Dead Sea sediments.” Geochemistry, Geophysics, Geosystems, Pp. e2021GC009665. Publisher's Version
Ayana Neta, Roni Gafni, Hilit Elias, Nitsan Bar-Shmuel, Liora Shaltiel-Harpaz, Efrat Morin, and Shai Morin. 2021. “Decision support for pest management: Using field data for optimizing temperature-dependent population dynamics models.” Ecological Modelling, 440, July 2020, Pp. 109402. Publisher's Version Abstract
Insect physiology is highly dependent on the environmental temperature, and the relationship can be mathematically defined. Thus, many models that aim to predict insect-pest population dynamics, use meteorological data as input to descriptive functions that predict the development rate, survival and reproduction of pest populations. In most cases, however, these functions/models are laboratory-driven and are based on data from constant-temperature experiments. Therefore, they lack an important optimization and validation steps that test their accuracy under field conditions. Here, we developed a realistic and robust regional framework for modeling the field population dynamics of the global insect pest Bemisia tabaci. First, two non-linear functions, development rate (DR) and female reproduction (EN) were fitted to data collected in constant temperature experiments. Next, nine one-generation field experiments were conducted in order to establish a field-derived database of insect performance, representing a variety of growing conditions (different seasons, regions and host plants). Then, sensitivity analyses were performed for identifying the optimal time-scale for which the running-averaged temperatures should be fed to the model. Setting the time to 6 h (i.e., each of the 24-time steps per day represents the last 6 h average) produced the best fit (RMSD score of 1.59 days, 5.7% of the mean) between the field observations and the model simulations. We hypothesize that the 6 h ‘relevant biological time-scale' captures the insect's physiological memory of daily cycling temperature events. Lastly, we evaluated the potential of the developed modeling framework to serve as a decision support tool in pest-management programs by correlating the model predictions with field-observations of three pest control inspectors during 2019. The model successfully predicted the first notable appearance of the insect in the field (completion of the third generation in May). Also, the model correctly identified the sharp rise in abundance (outbreak point) in mid-July (completion of the fifth generation), and the persistent rise in abundance through August and September. Comparing the simulations of the 2018 and 2019 seasons indicated that the model can also serve as a tool for retrospective systematic assessment of major decisions. Taken together, these data demonstrate the model robustness and its potential to provide an excellent decision-making support platform in regional control of pest species.
Asaf Zussman Esteban F. Klor. 2021. “Defense and the Economy in Israel, 1990-2016.” In The Israeli Economy in the Last Twenty Years: Lights and Shadows in a Market Economy, Pp. 168-202. New York: Cambridge University Press.
Full Text
Determining the structure and binding mechanism of oxytocin-Cu(2+) complex using paramagnetic relaxation enhancement NMR analysis
I. Alshanski, D. E. Shalev, S. Yitzchaik, and M. Hurevich. 2021. “Determining the structure and binding mechanism of oxytocin-Cu(2+) complex using paramagnetic relaxation enhancement NMR analysis.” J Biol Inorg Chem. Abstract

Oxytocin is a neuropeptide that binds copper ions in nature. The structure of oxytocin in interaction with Cu2+ was determined here by NMR, showing which atoms of the peptide are involved in binding. Paramagnetic relaxation enhancement NMR analyses indicated a binding mechanism where the amino terminus was required for binding and subsequently Tyr2, Ile3 and Gln4 bound in that order. The aromatic ring of Tyr2 formed a π-cation interaction with Cu2+. Oxytocin copper complex structure revealed by paramagnetic relaxation enhancement NMR analyses.

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Alshanski I., Shalev D. E., Yitzchaik S., and Hurevich M. 2021. “Determining the structure and binding mechanism of oxytocin-Cu2+ complex using paramagnetic relaxation enhancement NMR analysis.” J. Biol. Inorg. Chem. Link Abstract

 

Oxytocin is a neuropeptide that binds copper ions in nature. The structure of oxytocin in interaction with Cu2+ was determined here by NMR, showing which atoms of the peptide are involved in binding. Paramagnetic relaxation enhancement NMR analyses indicated a binding mechanism where the amino terminus was required for binding and subsequently Tyr2, Ile3 and Gln4 bound in that order. The aromatic ring of Tyr2 formed a π-cation interaction with Cu2+.

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Falsi L., Aversa M., F. Di Mei, D Pierangeli, Xin F., A.J. Agranat, and E. DelRe. 2021. “Direct observation of fractal-dimensional percolation in the 3D cluster dynamics of a ferroelectric super-crystal.” Phys. Rev. Lett. , 126, 037601.
A. Y. Strauss, I. Fradkin, and J.D Huppert. 2021. “Disentangling doubt and checking behaviors and examining their association with obsessive compulsive symptoms.” Clinical Psychological Science, 9, 5, Pp. 850-865.
Diversity in News Recommendations
Avraham Bernstein, Claes H. de Vreese, Natali Helberger, Wolfgang Schulz, Katharina Zweig, Christian Baden, Michael A. Beam, Marc P. Hauer, Lucien Heitz, Pascal Jürgens, Christian Katzenbach, Benjamin Kille, Beate Klimkiewicz, Wiebke Loosen, Judith Moeller, Goran Radanovic, Guy Shani, Nava Tintarev, Suzanne Tolmeijer, Wouter Van Atteveldt, Sanne Vrijenhoek, and Theresa Zueger. 2021. “Diversity in News Recommendations.” Dagstuhl Manifestos, 9, 1, Pp. 43-61. Publisher's Version Abstract

News diversity in the media has for a long time been a foundational and uncontested basis for ensuring that the communicative needs of individuals and society at large are met. Today, people increasingly rely on online content and recommender systems to consume information challenging the traditional concept of news diversity. In addition, the very concept of diversity, which differs between disciplines, will need to be re-evaluated requiring a interdisciplinary investigation, which requires a new level of mutual cooperation between computer scientists, social scientists, and legal scholars. Based on the outcome of a multidisciplinary workshop, we have the following recommendations, directed at researchers, funders, legislators, regulators, and the media industry: 1. Do more research on news recommenders and diversity. 2. Create a safe harbor for academic research with industry data. 3. Optimize the role of public values in news recommenders. 4. Create a meaningful governance framework. 5. Fund a joint lab to spearhead the needed interdisciplinary research, boost practical innovation, develop. reference solutions, and transfer insights into practice.

Anupam Sadhu, Monika Rai, Teddy Salim, Xin Jin, Joel Ming Rui Tan, Shin Woei Leow, Mahmoud G. Ahmed, Shlomo Magdassi, Subodh G. Mhaisalkar, and Lydia Helena Wong. 2021. “Dual Role of Cu‐Chalcogenide as Hole‐Transporting Layer and Interface Passivator for p–i–n Architecture Perovskite Solar Cell (Adv. Funct. Mater. 38/2021).” Advanced Functional Materials, 31, 38, Pp. 2170282 - 2170282. Publisher's Version Abstract
Hole-Transporting Layers In article number 2103807, Lydia Helena Wong and co-workers use Al-doped CuS as a hole transport layer (HTL) for perovskite solar cells. Here, it has been demonstrated that, due to the interaction between sulfur and lead, better perovskite crystallization takes place at the interface. Because of this improved interface quality, the sulfide-HTL based devices outperform the oxide HTL-based devices in terms of ambient stability.
Alshanski I., Shitrit A., Sukhran Y., Unverzagt C., Hurevich M., and Yitzchaik S. 2021. “Effect of Interfacial Properties on Impedimetric Biosensing of the Sialylation Process with a Biantennary N-Glycan-Based Monolayer.” Langmuir. Link Abstract

 

Sensing enzymatic sialylation provides new tools for the evaluation of pathological events and pathogen invasion. Enzymatic sialylation is usually monitored via fluorescence or metabolic labeling, which requires relatively large amounts of the glycan substrate with limited availability. Using a label-free biosensor requires smaller quantities of substrates because the interactions induce measurable changes to an interface, which can be translated into a signal. The downside of label-free biosensors is that they are very sensitive to changes at the interface, and the properties of the surface layer can play a major role. Electrochemical impedance spectroscopy was used here to follow the enzymatic sialylation of a biantennary N-glycan acceptor in mixed monolayers. The surfaces contained either neutral, positively or negatively charged, or zwitterionic functional groups. The systems were characterized by contact potential difference, ellipsometry, and contact angle analyses. We found that the characteristics of the mixed monolayer have a profound effect on the biosensing of the enzymatic sialylation. Positively charged layers were found to adsorb the enzyme under the reaction conditions. Negatively charged and zwitterionic surfaces were nonresponsive to enzymatic sialylation. Only the neutral mixed monolayers provided signals that were related directly to enzymatic sialylation. This work demonstrates the importance of appropriate interface properties for monitoring enzymatic sialylation processes.

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Yaelle Schilt, Tal Berman, Xiaohui Wei, Einat Nativ-Roth, Yechezkel Barenholz, and Uri Raviv. 2021. “Effect of the ammonium salt anion on the structure of doxorubicin complex and PEGylated liposomal doxorubicin nanodrugs.” Biochimica et Biophysica Acta (BBA) - General Subjects, 1865, 5, Pp. 129849. Publisher's Version Abstract

Background In Doxil®, PEGylated nanoliposomes are created by hydration of the lipids in ammonium sulfate, and are remotely loaded with doxorubicin by a transmembrane ammonium gradient. The ammonium sulfate is then removed from the external aqueous phase, surrounding the liposomes, and replaced by an isoosmotic sucrose solution in 10 mM histidine buffer at pH 6.5. Methods We prepared PEGylated liposomal doxorubicin (PLD) with a series of ammonium monovalent salts that after remote loading became the intraliposome doxorubicin counteranions. We analyzed the liposomes by solution X-ray scattering, differential scanning calorimetry, and electron micropscopy. Results PLDs prepared with sulfonic acid derivatives as counteranion exhibited chemical and physical stabilities. We determined the effect of these ammonium salt counteranions on the structure, morphology, and thermotropic behavior of the PEGylated nanoliposomes, formed before and after doxorubicin loading, and the bulk properties of the doxorubicin-counteranion complexes. By comparing the structure of the doxorubicin complexes in the bulk and inside the nanoliposomes, we revealed the effect of confinement on the structure and doxorubicin release rate for each of the derivatives of the ammonium sulfonic acid counteranions. Conclusions We found that the extent and direction of the doxorubicin confinement effect and its release rate were strongly dependent on the type of counteranion. The counteranions, however, neither affected the structure and thermotropic behavior of the liposome membrane, nor the thickness and density of the liposome PEG layers. In an additional study, it was demonstrated that PLD made with ammonium-methane sulfonate exhibit a much lower Hand and Foot syndrome. General significance The structure, physical state, and pharmacokinetics of doxorubicin in PEGylated nanoliposomes, prepared by transmembrane remote loading using gradients of ammonium salts, strongly depend on the counteranions.

Asaf Shemesh Sadeh, Raviv Dharan, Hiba Ghareeb, Norman Metanis, Israel Ringel, and Uri Raviv. 2021. “Effect of Tubulin Self-Association on GTP Hydrolysis and Nucleotide Exchange Reactions.” ChemRxiv. Publisher's Version

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